Rapid Mining of Novel α-Glucosidase and Lipase Inhibitors from Streptomyces sp. HO1518 Using UPLC-QTOF-MS/MS

Mar Drugs. 2022 Mar 4;20(3):189. doi: 10.3390/md20030189.

Abstract

A rapid and sensitive method using ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS) was applied for the analysis of the metabolic profile of acarviostatin-containing aminooligosaccharides derived from Streptomyces sp. HO1518. A total of ninety-eight aminooligosaccharides, including eighty potential new compounds, were detected mainly based on the characteristic fragment ions originating from quinovosidic bond cleavages in their molecules. Following an LC-MS-guided separation technique, seven new aminooligosaccharides (10-16) along with four known related compounds (17-20) were obtained directly from the crude extract of strain HO1518. Compounds 10-13 represent the first examples of aminooligosaccharides with a rare acarviostatin II02-type structure. In addition, all isolates displayed considerable inhibitory effects on three digestive enzymes, which revealed that the number of the pseudo-trisaccharide core(s), the feasible length of the oligosaccharides, and acyl side chain exerted a crucial influence on their bioactivities. These results demonstrated that the UPLC-QTOF-MS/MS-based metabolomics approach could be applied for the rapid identification of aminooligosaccharides and other similar structures in complex samples. Furthermore, this study highlights the potential of acylated aminooligosaccharides with conspicuous α-glucosidase and lipase inhibition for the future development of multi-target anti-diabetic drugs.

Keywords: Streptomyces sp. HO1518; UPLC-QTOF-MS/MS; aminooligosaccharides; diabetes; digestive enzyme inhibitors; metabolic profiling.

MeSH terms

  • Chromatography, High Pressure Liquid
  • Glycoside Hydrolase Inhibitors / chemistry*
  • Lipase / antagonists & inhibitors*
  • Oligosaccharides / chemistry*
  • Pancreatic alpha-Amylases / antagonists & inhibitors*
  • Streptomyces / chemistry*
  • Sucrase / antagonists & inhibitors*
  • Tandem Mass Spectrometry
  • alpha-Glucosidases / chemistry

Substances

  • Glycoside Hydrolase Inhibitors
  • Oligosaccharides
  • Lipase
  • Pancreatic alpha-Amylases
  • alpha-Glucosidases
  • Sucrase